Phenotypes Associated with This Genotype

Genotype
MGI:6849976

• Allelic Composition: Pla2g6^tm1.1Hlw/Pla2g6^tm1.1Hlw
• Genetic Background: involves: 129 * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

impaired coordination ( J:317126 )

• 6- to 12-month-old mice exhibit impaired motor coordination, with a reduction in retention time on the rotarod

decreased vertical activity ( J:317126 )

• 6- to 12-month-old mice exhibit a decrease in the number of rears

decreased locomotor activity ( J:317126 )

• 6- to 12-month-old mice exhibit early-onset and progressive decrease in the locomotion activity, including velocity and distance

• mice treated with methyl L-DOPA show rescue of hypoactivity

bradykinesia ( J:317126 )

• 6- to 12-month-old mice exhibit an increase in time required to perform the pole test, indicating impaired motor performance and bradykinesia

nervous system

abnormal substantia nigra pars compacta morphology ( J:317126 )

• the number of TH+ SNpc dopaminergic neurons is reduced in 6- and 9-month-old mice, but not in 3-month old mice, indicating early-onset degeneration of these neurons

abnormal synaptic bouton morphology ( J:317126 )

• mice exhibit reduced radiotracer striatal uptake at 6 and 9 months of age, but not at 3 months of age and the density of striatal TH staining is decreased at 9 months of age, indicating loss of nigrostriatal dopaminergic terminals

neuron degeneration ( J:317126 )

• mice exhibit early-onset degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurons

• however, neuronal loss is not seen in the striatum, hippocampus, or cerebral cortex

Lewy bodies ( J:317126 )

• mice exhibit Lewy bodies in the substantia nigra at 9 months of age

cellular

abnormal mitochondrial morphology ( J:317126 )

• mice exhibit mitochondrial degeneration in SNpc dopaminergic neurons

abnormal mitochondrial crista morphology ( J:317126 )

• neuromelanin organelle-containing SNpc dopaminergic neurons show mitochondria with disrupted cristae

decreased mitochondrial size ( J:317126 )

• neuromelanin organelle-containing SNpc dopaminergic neurons show smaller mitochondrial size

abnormal mitophagy ( J:317126 )

• autophagy/mitophagy-related protein levels are decreased in the substantia nigra, indicating impaired mitophagy

increased endoplasmic reticulum stress ( J:317126 )

• mice show increased endoplasmic reticulum (ER) stress in the substantia nigra as indicated by increased levels of ER-stress proteins

abnormal mitochondrial physiology ( J:317126 )

• activity of mitochondrial complex I or III is reduced in the substantia nigra

• mice show a reduced level of intracellular ATP production in the substantia nigra

• mice exhibit an overproduction of ROS, increased level of lipid peroxidation of mitochondria, and upregulated cytosolic level of cytochrome c in the substantia nigra, indicating further mitochondrial dysfunction

• level of cytosolic cytochrome c, active caspase-9 and active caspase 3 are increased in the substantia nigra at 9 months of age, indicating activation of mitochondrial apoptotic pathway

• however, activity of mitochondrial complex II or IV is not altered

oxidative stress ( J:317126 )

• mice exhibit an overproduction of reactive oxygen species (ROS) in the substantia nigra

homeostasis/metabolism

abnormal mitophagy ( J:317126 )

• autophagy/mitophagy-related protein levels are decreased in the substantia nigra, indicating impaired mitophagy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 14		DOID:0060900	OMIM:612953	J:317126